The cytotoxic effects of regorafenib in combination with protein kinase D inhibition in human colorectal cancer cells.

摘要: // Ning Wei 1,2 , Edward Chu Shao-yu Wu Peter Wipf 2,3 and John C. Schmitz 1 Division of Hematology-Oncology, Department Medicine, University Pittsburgh School Pittsburgh, PA, USA 2 Cancer Therapeutics Program, Institute, 3 Chemistry, Correspondence: Wei, email: Keywords : protein kinase D, regorafenib, human colorectal cancer, apoptosis, NF-κB Received August 12, 2014 Accepted December 02, Published 03, Abstract Metastatic cancer (mCRC) remains a major public health problem, diagnosis metastatic disease is usually associated with poor prognosis. The multi-kinase inhibitor regorafenib was approved in 2013 the U.S. for treatment mCRC patients who progressed after standard therapies. However, clinical efficacy quite limited. One potential strategy to improve therapy combine agents that target key cellular signaling pathways, which may lead synergistic enhancement antitumor overcome drug resistance. Protein D (PKD), family serine/threonine kinases, mediates pathways implicated multiple processes. Herein, we evaluated combination PKD several CRC cells. Using Chou-Talalay model, index values this demonstrated effects on inhibition cell proliferation clonal formation. This resulted induction apoptosis as determined by flow cytometry, increased PARP cleavage, decreased activation anti-apoptotic HSP27. also yielded enhanced ERK, AKT, signaling. Taken together, appears be promising mCRC.